NM_000478.6(ALPL):c.522del (p.Ser175fs) AND not provided

This record was updated by the submitter. Please see the current version.

Germline classification:: Pathogenic/Likely pathogenic (3 submissions)
Last evaluated:: Dec 26, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000710515.14

Allele description

NM_000478.6(ALPL):c.522del (p.Ser175fs)

Gene:

ALPL:alkaline phosphatase, biomineralization associated [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

1p36.12

Genomic location:

Preferred name:

NM_000478.6(ALPL):c.522del (p.Ser175fs)

HGVS:

NC_000001.11:g.21564090del
NG_008940.1:g.59726del
NM_000478.6:c.522delMANE SELECT
NM_001127501.4:c.357del
NM_001177520.3:c.291del
NM_001369803.2:c.522del
NM_001369804.2:c.522del
NM_001369805.2:c.522del
NP_000469.3:p.Ser175fs
NP_001120973.2:p.Ser120fs
NP_001170991.1:p.Ser98fs
NP_001356732.1:p.Ser175fs
NP_001356733.1:p.Ser175fs
NP_001356734.1:p.Ser175fs
NC_000001.10:g.21890579del
NC_000001.10:g.21890583del
NM_000478.4:c.522del
NM_000478.4:c.522delC
NM_000478.5:c.522del
NM_000478.5:c.522delC

Protein change:

S120fs

Links:

dbSNP: rs750174638

NCBI 1000 Genomes Browser:

rs750174638

Molecular consequence:

NM_000478.6:c.522del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001127501.4:c.357del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001177520.3:c.291del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001369803.2:c.522del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001369804.2:c.522del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001369805.2:c.522del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

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Genome Links for Gene (Select 312132) (1)
Genome
transmembrane protein 106B isoform X1 [Rattus norvegicus]
transmembrane protein 106B isoform X1 [Rattus norvegicus]
gi|1958769275|ref|XP_038963435.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000840753	Athena Diagnostics	criteria provided, single submitter (Athena Diagnostics Criteria)	Likely pathogenic (Dec 21, 2017)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001210179	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 26, 2023)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 3174660, 10679946, 32973344, 33814268, 28492532
SCV002018184	Revvity Omics, Revvity	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Mar 6, 2020)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000840753

Athena Diagnostics

criteria provided, single submitter

(Athena Diagnostics Criteria)

Likely pathogenic
(Dec 21, 2017)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

SCV001210179

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 26, 2023)

germline

clinical testing

PubMed (5)
[See all records that cite these PMIDs]

SCV002018184

Revvity Omics, Revvity

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Mar 6, 2020)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

A Standardized DNA Variant Scoring System for Pathogenicity Assessments in Mendelian Disorders.

Karbassi I, Maston GA, Love A, DiVincenzo C, Braastad CD, Elzinga CD, Bright AR, Previte D, Zhang K, Rowland CM, McCarthy M, Lapierre JL, Dubois F, Medeiros KA, Batish SD, Jones J, Liaquat K, Hoffman CA, Jaremko M, Wang Z, Sun W, Buller-Burckle A, et al.

Hum Mutat. 2016 Jan;37(1):127-34. doi: 10.1002/humu.22918. Epub 2015 Oct 29.

PubMed [citation]

PMID:: 26467025
PMCID:: PMC4737317

A missense mutation in the human liver/bone/kidney alkaline phosphatase gene causing a lethal form of hypophosphatasia.

Weiss MJ, Cole DE, Ray K, Whyte MP, Lafferty MA, Mulivor RA, Harris H.

Proc Natl Acad Sci U S A. 1988 Oct;85(20):7666-9.

PubMed [citation]

PMID:: 3174660
PMCID:: PMC282253

See all PubMed Citations (7)

Details of each submission

From Athena Diagnostics, SCV000840753.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Invitae, SCV001210179.6

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

This sequence change creates a premature translational stop signal (p.Ser175Alafs*23) in the ALPL gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ALPL are known to be pathogenic (PMID: 3174660, 10679946, 32973344, 33814268). This variant is present in population databases (rs750174638, gnomAD 0.009%). This variant has not been reported in the literature in individuals affected with ALPL-related conditions. ClinVar contains an entry for this variant (Variation ID: 371067). For these reasons, this variant has been classified as Pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Revvity Omics, Revvity, SCV002018184.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Jun 17, 2024

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